Chemistry Reference
In-Depth Information
Info Box
The development of a glyco-compound into a successful pharmaceutical to be
used in man is a long process and involves several steps. The initial drug dis-
covery phase, during which activity against a particular target molecule is veri-
fi ed, is followed by extensive preclinical and clinical development programs.
The main purpose of preclinical testing is to determine a drug's pharmaco-
dynamics (effects of the drug on the organism), pharmacokinetics (processing
of the drug in the organism), absorption, distribution, metabolism and excre-
tion, and toxicity (including carcinogenicity and effects on mammalian repro-
duction) in animals before testing on humans ensue. Further, a recommended
starting dose and dose scheme is established during the preclinical
development.
The clinical development program includes phase 0, I, II, III and IV trials.
Phase 0, or fi rst - in - man trials, involves administrating single subtherapeutic
doses of the drug to a small number (10-15) of subjects with the purpose of
acquiring pharmacokinetics and pharmacodynamics data. In phase I studies,
small groups of less than 100 healthy subjects are exposed to the drug in order
to assess safety, tolerability, pharmacokinetics and pharmacodynamics of the
drug. One important purpose of the phase I trial is to fi nd the drug's appropri-
ate therapeutic dose. Most drugs under development fail in phase II, which is
set up to assess effi cacy and safety in a larger group of between 20 and 300
patients. Phase III studies are usually multicenter trials on thousands of
patients with the purpose of comparing the study drug's effi cacy with that of
the most effective treatment currently used. These studies are the most expen-
sive and time-consuming trials to run. For some drugs at least two successful
phase III trials are required in order to get approval from regulatory agencies.
Postmarketing surveillance or phase IV trials involves further safety and effi -
cacy assessment on certain patient groups (for example pregnant women or
patients with other ongoing pharmacological treatments), and are performed
after the drug has received approval and is available on the market.
Drug development is a time-consuming process. Preclinical development
may well take at least 5 years before the drug is even tested on humans and
clinical development takes on average 8 years from its initiation until the drug
is approved for sale.
administration of the sugar ligand in excess in a soluble form should form a
complex with the microbe preventing it from binding to the cell surface (please
see also Figure 4.3). The idea of a therapy based on an anti- adhesion strategy has
been around for several decades and is known to work in breastfed children. Breast
milk, with its richness in oligosaccharides and glycosylated proteins, is known to
have antimicrobial activity, which is partly explained by glycan-mediated inhibition
of microbial adhesion.
